VIDAZA- azacitidine injection, powder, lyophilized, for solution
Celgene Corporation
1 INDICATIONS AND USAGE
1.1 Myelodysplastic Syndromes (MDS)
VIDAZA� is indicated for treatment of patients with the following French-American-British (FAB) myelodysplastic syndrome subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL).
2 DOSAGE AND ADMINISTRATION
2.1 First Treatment Cycle
The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days. Premedicate patients for nausea and vomiting.
Obtain complete blood counts, liver chemistries and serum creatinine prior to the first dose.
2.2 Subsequent Treatment Cycles
Repeat cycles every 4 weeks. The dose may be increased to 100 mg/m2 if no beneficial effect is seen after 2 treatment cycles and if no toxicity other than nausea and vomiting has occurred. It is recommended that patients be treated for a minimum of 4 to 6 cycles. However, complete or partial response may require additional treatment cycles. Treatment may be continued as long as the patient continues to benefit
3 DOSAGE FORMS AND STRENGTHS
VIDAZA (azacitidine for injection) is supplied as lyophilized powder in 100 mg single-dose vials.
4 CONTRAINDICATIONS
4.1 Advanced Malignant Hepatic Tumors
VIDAZA is contraindicated in patients with advanced malignant hepatic tumors [see Warnings and Precautions (5.2)].
4.2 Hypersensitivity to Azacitidine or Mannitol
VIDAZA is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol.
DESCRIPTION
VIDAZA (azacitidine for injection) contains azacitidine, which is a pyrimidine nucleoside analog of cytidine. Azacitidine is 4-amino-1-β-D-ribofuranosyl-s-triazin-2(1H)-one
The empirical formula is C8 H12 N4 O5. The molecular weight is 244. Azacitidine is a white to off-white solid. Azacitidine was found to be insoluble in acetone, ethanol, and methyl ethyl ketone; slightly soluble in ethanol/water (50/50), propylene glycol, and polyethylene glycol; sparingly soluble in water, water saturated octanol, 5% dextrose in water, N-methyl-2-pyrrolidone, normal saline and 5% Tween 80 in water; and soluble in dimethylsulfoxide (DMSO).
The finished product is supplied in a sterile form for reconstitution as a suspension for subcutaneous injection or reconstitution as a solution with further dilution for intravenous infusion. Vials of VIDAZA contain 100 mg of azacitidine and 100 mg mannitol as a sterile lyophilized powder.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
VIDAZA is a pyrimidine nucleoside analog of cytidine. VIDAZA is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of azacitidine required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis. Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. The cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non-proliferating cells are relatively insensitive to azacitidine.
HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
VIDAZA (azacitidine for injection) is supplied as a lyophilized powder in 100 mg single-dose vials packaged in cartons of 1 vial (NDC 59572-102-01).
Storage
Store unreconstituted vials at 25� C (77� F); excursions permitted to 15�-30� C (59�-86� F) (See USP Controlled Room Temperature).
Handling and Disposal
VIDAZA is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1
17 PATIENT COUNSELING INFORMATION
Hepatotoxicity in Patients with Severe Pre-Existing Hepatic Impairment
Instruct patients to inform their physician about any underlying liver disease [see Warnings and Precautions (5.2)].
Renal Toxicity
Instruct patients to inform their physician about any underlying renal disease [see Warnings and Precautions (5.3) and Use in Specific Populations (8.6)].
Embryo-Fetal Risk
Advise pregnant women of the potential risk to a fetus [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1)].
Advise females of reproductive potential to avoid pregnancy during treatment with VIDAZA. Advise males with female sexual partners of reproductive potential to not father a child and to use effective contraception during treatment with VIDAZA. Advise patients to report pregnancy to their physicians immediately
